Diffuse Parenchymal Lung Disease
ACOI Board Review 2012
Thomas F. Morley, DO, MACOI, FCCP, FAASM
Professor of Medicine
Chairman Department of Internal Medicine
Director of the Division of Pulmonary, Critical Care and Sleep Medicine
Rowan University - SOM
No Disclosures
Restrictive Lung DiseasesBy Category
1. Lung Fibrosis
2. Thoracic Deformity
3. Massive effusion
4. Respiratory muscle weakness
5. Increased abdominal pressure
6. Extrinsic Compression
Mnemonic for RestrictionPAINT
• Pleural Disease
• Alveolar filling
• Interstitial
• Neuromuscular
• Thoracic
ILD = Misnomer
• Most of these disease are not restricted to the “interstitium” of the lung
• It is actually a radiographic term to differentiate it from alveolar filling diseases
• Diffuse Parenchymal Lung Disease is a better term
The interstitium is the scant space between the capillary endothelial cell and the lung epithelium. It also includes the space that airways, blood vessel, and lymphatics traverse.
Diffuse Parenchymal Lung DiseaseCharacteristics
1. Diffuse infiltrates bilaterally
2. Restrictive Physiology
3. Histologic distortion of gasexchange areas
4. Dyspnea (exercise desat) andcough
COMMONLESS
COMMON
Sarcoidosis Langerhans Cell Histiocytosis
(aka, EG, HX)
IPF (aka cryptogenic Hypersensitivity Pneumonitis
fibrosing alveolitis
COP Collagen Vascular Diseases
Lymphangetic Spread of CA (RA, SLE, MCTD, PSS)
Pneumoconiosis Granulomatous vasculitis
Drug-induced Goodpasture's syndrome
Chronic Eosinophilic Pneumonia Alveolar proteinosis
Differential Diagnosis of DPLD
Pathogenesis of InterstitialLung Diseases
Inhaled Stimulus
Blood BorneStimulus
Alveolitis
Recruitment of Inflammatory Cells
TISSUE DAMAGE
HEALING FIBROSIS
Approach to DPLDSlide 1
1. Characteristics of Presenting Illness Duration of Symptoms
Rate of Progression
Fever
Hemoptysis
Extrathoracic manifestations
2. Exposures Pneumoconiosis
Hypersensitivity
Drug-induced
Occupational
IV drug use
Approach to DPLDSlide 2
3. Physical Exam Crackles
Thoracic Wheeze
Rub
Normal
Extrathoracic Nodes
Skin
Joints
CNS
Eyes
Approach to DPLDSlide 3
4. Laboratory (All) CBC with Diff
UA/Creatinine
CRP, RF, ANA
ACE level
If H+P Suggestive:ANCA-c (granulomatosis
with polyangitis)RNP (MCTD)
Anti-GBM (Goodpasture's)
Serologic Tests Can Help ExcludeOther Conditions
Connective tissue diseases
Hypersensitivity panel
(if exposure history)Hypersensitivity
pneumonitis
CRP
ANA
CCP (for RA) Cyclic Citrullinated Peptide Antibody
CK
Aldolase
Anti-myositis panel with Jo-1 antibody
ENA panel– Scl-70 – SSc (topoisomerase I)
– Ro (SSA) - Sjgorens
– La (SSB)
– Smith -Lupus
– RNP - MCTD
ATS/ERS. Am J Respir Crit Care Med. 2000;161:646-664.
Approach to DPLDSlide 4
Adenopathy Nodules
5. X-Ray Sarcoidosis Sarcoidosis
Patterns Reticular Silicosis Rheumatoid Arthritis
Reticulonodular BerylliosisGranulomatosis with
PolyangitisNodular Langerhans cell
granulomatosisGround Glass Sjogren's
Distribution
Upper Lobe Silicosis
Sarcoidosis
Langerhans Cell Gran.
Ankylosing spondylitis
Lower Lobe IPF
Rheumatoid arthritis
Asbestosis
PSS
Sjogren's
Pleural AsbestosRASLE
Approach to DPLDSlide 5
6. PFT Spirometry
Lung volumes
DLCO
ABG
7. Tissue Transbronchial Biopsy
Thoracoscopy
Open lung biopsy
Extrathoracic sites
BAL ?
Gallium Scan ?
Symptom Duration inDPLD
Chronic Acute/Subacute
IPF BOOP/COP
Rheumatoid Lung Drug-induced
Sarcoidosis Hypersensitivity
Langerhans Cell
GranulomatosisChemical exposure
Pneumoconiosis
Extrathoracic Manifestations ofDPLD (1)
Nasal symptoms Wegener's Granulomatosis
Arthritis RA
Sarcoidosis
CVD
Sjogren's syndrome
Skin Sarcoidosis
CVD
Granulomatous vasculitis
Dermatomyositis
PSS
Extrathoracic Manifestations ofDPLD (2)
CNS CVD
Sarcoidosis
Lymphomatoid granulomatosis
Muscle Sarcoidosis
Polymyositis
GI PSS
Polymyositis
Renal Granulomatosis with polyangitis
CVD
Goodpasture's
PSS
CASE 1
34 y.o. black, female presentswith 6 months of non-productiveCOUGH, and DYSPNEA with exertion
NO MEDS or IVDA
NO OCCUPATIONAL EXPOSURES
NO SYSTEMIC SIGNS OR SYMPTOMS
SARCOIDOSIS
SarcoidosisX-ray Findings at Presentation
STAGE FINDINGS PERCENT
O Normal 5
I BHA 50
II BHA + Lung 30
III Lung Only 15
IV Fibrosis ?
BHA: Sarcoidosis
35 yomale
Sarcoidosis
Stage 2 sarcoidosispre-tx
Stage 2 sarcoidosis
2 years post-tx
Adultfemale
NodularSarcoidosis
Stage 3
Sarcoidosis
Multisystem disease of unknown etiologyNoncaseating granuloma are characteristicNOT DIAGNOSTIC
Lung is the most common organ systeminvolved (94%)
Peak onset 2nd and 3rd decades
10 to 17 times more prevalent in blacks
SarcoidosisGallium scan does NOT correlatewith need for or response to TX.
LAB: ACE, LFT's, Calcium, UAhypergammaglobulinemia (68 %)
Anergy (43 to 66 %)
Dx: Transbronchial lung biopsy (TBLBx)is adequate for Dx 80 to 90 %.BAL - lymphocytic
Tx: Steroids
Noncaseating Granulomas
Diagnosis of SarcoidosisTHREE ELEMENTS
1. Compatible clinical picture
2. Noncaseating granulomas in tissue
3. Negative culture/stains for AFB andfungi
CASE 260 y.o. white, male severeexertional dyspnea over 3 to 4years. Non-productive coughis noted.
Viral prodrome prior toinitial symptoms.
Nonsmoker, no meds, no occupationalexposures, No high risk behaviors
EXAM - Crackles, digital clubbing
IPF
IdiopathicPulmonary Fibrosis
IPF
Idiopathic Pulmonary FibrosisAKA Cryptogenic Fibrosing Alveolitis
Older age (> 60 Y.O.), M sl > F
Slow progression over 2 or moreyears.
Non-productive cough, dyspnea
Clubbing 50-90 % of patients
– Incidence: > 30,000 patients/year
– Prevalence: > 80,000 current patients
– Age of onset: most 40–70 years
– Two-thirds > 60 years old at presentation
– Males > females
ATS/ERS. Am J Respir Crit Care Med. 2000;161:646-664.
Raghu G, et al. Am J Respir Crit Care Med. 2006;174:810-816.
US Demographics of IPF
0
50
100
150
200
250
300
45-54 55-64 65-74 75+
Male
Female
0
20
40
60
80
100
120
45-54 55-64 65-74 75+
Male
Female
PrevalenceIncidence
Per
10
0,0
00
Per
10
0,0
00
Tx for IPF50 % mortality at 5 years
10 % develop bronchogenic CA
Nintedanib, (OFEV) a receptor blocker for
multiple tyrosine kinases that mediate
elaboration of fibrogenic growth factors
Pirfenidone (Espiert) is an antifibrotic agent
that inhibits transforming growth factor beta
(TGF-b)-stimulated collagen synthesis,
decreases the extracellular matrix, and blocks
fibroblast proliferation in vitro
Transplant
Idiopathic Pulmonary FibrosisDiagnosis
X-ray shows bilateral reticularor reticulonodular infiltrateswith lower lobe distribution
HRCT -subpleural septal thickening
Lab: non-specific
Classically Open lung biopsy is requiredfor definitive diagnosis
Current Definition of IPF
• Distinct chronic fibrosing
interstitial pneumonia
• Unknown cause
• Limited to the lungs
• Has typical HRCT findings
• Associated with a histologic
pattern of UIP
ATS/ERS Consensus Statement. Am J Respir Crit Care Med.
2002;165:277-304.
Diagnostic Criteria for IPF Without a Surgical Lung Biopsy
Major Criteria
• Exclusion of other known causes of ILD
• Evidence of restriction and/or impaired gas
exchange
• HRCT: bibasilar reticular abnormalities with
minimal ground-glass opacities (honeycombing
is characteristic*)
• TBB or BAL that does not support an
alternative diagnosis
*Not included in current guidelines
ATS/ERS. Am J Respir Crit Care Med. 2000;161:646-664.
• All major criteria and at least 3 minor criteria must be present to
increase the likelihood of an IPF diagnosis
• Criteria currently under revision (2009)
Minor Criteria
• Age > 50 years
• Insidious onset of otherwise
unexplained dyspnea on exertion
• Duration of illness > 3 months
• Bibasilar, inspiratory, Velcro®
crackles
IPF - H+E stain
IPF (trichrome stain)
CASE 343 y.o. white female presentedwith 2 months of fever, cough,dyspnea, and 12 lbs wt loss
No meds, 20 P-Y smoker
No occupational exposures
No high risk behavior
Exam: 100 temp, cracklesupper lobes
CEP
Chronic Eosinophilic Pneumonia
Chronic Eosinophilic Pneumonia
Chronic Eosinophilic Pneumonia
Peak 3rd decade, 2:1 F:M
Subacute presentation over monthscough, fever, dyspnea, wt loss
X-ray - bilateral upper lobe infiltratesPERIPHERAL distribution (esp HRCT)
Blood, biopsy, BAL all with eosinophilia
Dramatic improvement with steroids(maintain for 6 months)
Drug-inducedInterstitial Lung Disease
Antirheumatics Gold
Penicillamine
Methotrexate
Antineoplastics Bleomycin
Cyclophosphamide
Mitomycin
Arrhythmics Amiodarone
Radiation
Oxygen
Illicit Drugs Talc
cocaine
Collagen Vascular Diseaseswith ILD
RA
PSS
Polymyositis/Dermatomyositis
MCTD
LUPUS
pulmonary fibrosis due toRA
CASE 4
47 y.o. homosexual male with11 month Hx of non-productivecough, fever, sweats, wheezing
Also 35 lbs wt loss over 6 months
EXAM: fever, basilar cracklesNo clubbing
BOOP/COP
CTCOP (BOOP)
Subpleural
Groundglassinfiltrates
Cryptogenic Organizing Pneumonia (BOOP)
Idiopathic
Viral
CVD
Drugs
Gas
Transplant
AIDS
Cryptogenic Organizing Pneumonia
Patient with patchy alveolar infiltrateswho does not improve following antibiotics
4th to 6th decade - subacute 2 -10 wk present
Fever, dry cough, following flu-like illnessMyalgia, headache, malaise are common
X-ray shows bilateral infiltrates,10 % reticularPeripheral distribution on HRCT
Cryptogenic Organizing Pneumonia
PathologyIntraluminal fibrosis with connectivetissue plugs in the respiratorybronchioles, alveolar ducts, andalveoli
Open lung Bx - NOT NECESSARYTBLBx and BAL are adequate
Steroid Responsive3 to 6 months TxRecurrence common if Tx stoppedtoo early
CASE 5
53 y.o. white male progressivedyspnea over 1 year. Some coughwith yellow Sputum
Heavy Smoker
Occupation: tombstones engraver
EXAM: decreased breath soundsdigital clubbing
SILICOSIS/PMF
56 yoMale
AnthracosisPMF
56 yo Male
AnthracosisPMF
Silicosis, PMF, Cavitation
Egg shellcalcification
PneumoconiosisInhaled Inorganic Dusts
1. Big ThreeAsbestosis, Anthracosis, Silicosis
2. Long gap between exposure and symptomsfrom ILD
3. Asbestos - Lower lobe reticular changesParietal pleural plaques
4. Anthracosis - Upper lobe nodules - PMF
5. Silicosis - Upper lobe nodules - PMFHilar adenopathyEgg shell calcification
Asbestosplaques
Hypersensitivity Pneumonitis
* Caused by repeated inhalation of anORGANIC dust or chemical - leads tosensitization
* Symptoms may be acute or chronic
* Fever, cough, dyspnea, and infiltratesoccur 4 to 6 hrs post exposureRepeated exposure leads to fibrosis
* Dx: depends on history and specificprecipitating antibodies to the antigen
Hypersensitivity Pneumonitis
* Type III - immune complex injury andType IV - delayed hypersensitivityis involved in pathology
* Acute pathology shows PMN infiltrate3 days later the infiltrate becomeslymphocytic and loose granulomasform. FOAMY histiocytes andbronchiolitis obliterans may be noted
Hypersensitivity Pneumonitis
Langerhans Cell HistiocytosisEG, HSC, and LS
All 3 disorders share a commonpathology (These terms have beenabandoned).
✓ Aggregations of abnormal histiocytes(Langerhans's cells)
Lung and bone are most often affectedwith UNIFOCAL disease
Multifocal disease - worse prognosis
26 yomale
LangerhansCell Histiocytosis
26 yomale
LCH
LangerhansCellHistiocytosis
LCHCLINICAL FEATURES
10 to 40 Y.O. M=F
Present with cough, fever, dyspnea,chest pain
10 % present with pneumothorax
X-ray - upper lobe cystic andreticulonodular changesNO VOLUME LOSS